rs5749468

chr22-32596403-T-Cchr22-32596403-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003490.4(SYN3):c.774+271A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,230 control chromosomes in the GnomAD database, including 3,020 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (3020 hom., cov: 32)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410

Genes affected

SYN3 (HGNC:11496): (synapsin III) This gene is a member of the synapsin gene family. Synapsins encode neuronal phosphoproteins which associate with the cytoplasmic surface of synaptic vesicles. Family members are characterized by common protein domains, and they are implicated in synaptogenesis and the modulation of neurotransmitter release, suggesting a potential role in several neuropsychiatric diseases. The protein encoded by this gene shares the synapsin family domain model, with domains A, C, and E exhibiting the highest degree of conservation. The protein contains a unique domain J, located between domains C and E. Based on this gene's localization to 22q12.3, a possible schizophrenia susceptibility locus, and the established neurobiological roles of the synapsins, this family member may represent a candidate gene for schizophrenia. The TIMP3 gene is located within an intron of this gene and is transcribed in the opposite direction. Alternative splicing of this gene results in multiple splice variants that encode different isoforms. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYN3	NM_003490.4	c.774+271A>G		intron_variant		ENST00000358763.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYN3	ENST00000358763.7	c.774+271A>G		intron_variant		5	NM_003490.4	P1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27111 AN: 152112 Hom.: 3014 Cov.: 32

Gnomad AFR AF: 0.0433

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.179

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.178 AC: 27117 AN: 152230 Hom.: 3020 Cov.: 32 AF XY: 0.181 AC XY: 13508 AN XY: 74430

Gnomad4 AFR AF: 0.0432

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.182

Alfa AF: 0.214 Hom.: 5255

Bravo AF: 0.174

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.95
Dann	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5749468; hg19: chr22-32992389;